PROJECT SUMMARY An estimated 5 million Americans suffer from Alzheimer?s disease (AD) which is a complex, multi-factorial disease of the brain. We observed that AD patients display a more robust expansion of innate cell populations in the cerebrospinal fluid than patients with the classic neuro-inflammatory disease, Multiple Sclerosis (MS)(35.0% vs 2.6%, AD:MS, p=0.002). Furthermore, AD patients display a decreased frequency of CD4+ T cells in the CSF compared to MS patients (37.8% vs 61.5%, AD:MS, p=0.01). These immune profile alterations in the CSF of AD patients was also observed in the blood. Thus, we hypothesize that expansion of innate immune cells and contraction of CD4+ T cells as observed in the CSF and periphery contributes to AD development by impacting antibody production against Abeta and Tau. To test this hypothesis, we will collect cerebrospinal fluid and peripheral blood from AD patients and age- matched HDs and analyze cellular and molecular aspects of the humoral immune compartment. The results of this study may support the expanded use of immune-stimulating therapies at an earlier stage of disease when they are most likely to be effective.